RESUMO
Background: Community pharmacies have changed during the COVID-19 pandemic, and new routines have been introduced to address the needs of customers and staff and to reduce the risk of spreading infection. Burnout has been described among staff possibly due to a changed working climate. However, little research has focused on the pandemic's effect on patient safety in community pharmacies. Objective: To examine pharmacists' perceptions of the impact of the COVID-19 pandemic on workload, working environment, and patient safety in community pharmacies. Methods: A survey was distributed to all Swedish community pharmacists, constituting a census study. Questions regarding the pharmacists' perception of the impact of the pandemic on workload, working environment, and patient safety were included. Respondents were asked to provide comments on their working situation. Quantitative results were analysed using descriptive statistics, and comments were analysed using qualitative content analysis. Results: The response rate was 41% (2034 responses). Most pharmacists (62%) considered the workload to be increased during the pandemic while work environment deteriorated (physical work environment was considered worse by 47% of respondents while psychosocial work environment was considered worse by 59%). Despite this, many respondents (55%) believed that patient safety was not affected. Neither having had COVID-19 nor being afraid of contracting it, influenced these perceptions in any substantial way. Findings were consistent regardless of education, professional role, number of years in community pharmacies, or special assignments in the pharmacies. According to the respondents, the communication within pharmacy companies during the pandemic was inadequate. Conclusions: The impact of the pandemic on working conditions is in line with previous findings but the effect on patient safety needs further studies. The respondents felt the management had a limited understanding of the conditions during the pandemic, which stresses the importance of good and clear communication during a crisis.
RESUMO
Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adiposidade/genética , Ácidos Graxos/metabolismo , Doenças Metabólicas/genética , Músculo Esquelético/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Regulação da Expressão Gênica , Resistência à Insulina/genética , Masculino , Doenças Metabólicas/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Oxirredução , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteínas de Sinalização YAPRESUMO
PURPOSE: To evaluate whether dexamethasone suppression treatment can improve (11) C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA). MATERIALS AND METHODS: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small "hot-spot" regions of interest comprising 4 pixels (SUVhs) and 1 pixel (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded. RESULTS: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to nonfunctional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p < 0.05), but tumour SUV was not significantly decreased after suppression in either PA or nonfunctional tumours (p > 0.05). However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p > 0.05). CONCLUSION: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series, dexamethasone-suppressed MTO-PET was unable to increase the tumour-to-normal adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.
Assuntos
Adenoma Adrenocortical/diagnóstico por imagem , Adenoma Adrenocortical/tratamento farmacológico , Dexametasona/uso terapêutico , Hiperaldosteronismo/diagnóstico por imagem , Hiperaldosteronismo/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Administração Oral , Adenoma Adrenocortical/patologia , Adulto , Idoso , Biópsia por Agulha , Relação Dose-Resposta a Droga , Esquema de Medicação , Etomidato/análogos & derivados , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/patologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos de Amostragem , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.
Assuntos
Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/patologia , Hiperaldosteronismo/etiologia , Adenoma/complicações , Adenoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adrenalectomia , Aldosterona/sangue , Análise de Variância , Causalidade , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/prevenção & controle , Hiperplasia/complicações , Hiperplasia/cirurgia , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipopotassemia/tratamento farmacológico , Hipopotassemia/etiologia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Renina/sangue , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: With an aging population, more patients might be treated for atherosclerotic renal artery stenosis (ARAS). The goal of this treatment is to achieve a dialysis-free life or a well-controlled blood pressure with reduced risks of cardiovascular complications. PURPOSE: To analyze the clinical outcome of percutaneous transluminal renal artery angioplasty without stenting (PTRA) or with stenting (PTRS) for ARAS at one center. MATERIAL AND METHODS: The study group comprised 152 patients who underwent 203 PTRA/PTRS. All had hypertension, and 45% had azotemia. A retrospective collection of baseline and postprocedural number of antihypertensive drugs, blood pressure, and serum creatinine were analyzed during a follow-up of 3-18 months. RESULTS: Technical success rate was 95%, and clinical benefit was seen in 63% of patients. Complications included a 30-day mortality rate of 1.5%, a total complication rate of 35%, and major adverse events in 13%. The major adverse events were highly related to azotemia. Major adverse events within 30 days, with permanent disability, were seen in 5% and almost exclusively in patients with moderate or severe renal impairment. A subgroup analysis of 28 patients with renal duplex resistive index (RI) pre-PTRA/S and 6 months' follow-up showed a benefit of PTRA/PTRS in 17 (68%) of the 25 patients with RI <80 and in all three (100%) of the patients with RI >or=80. CONCLUSION: Endovascular treatment of ARAS has an excellent technical success rate, with a clinical improvement rate of >60%. However, it is associated with a considerable complication rate. Serious complications are seen mainly in azotemic patients. Predictors of clinical response could not be identified. Renal duplex RI is questioned as a predictor of clinical outcome.
Assuntos
Angioplastia com Balão/métodos , Aterosclerose/terapia , Obstrução da Artéria Renal/terapia , Stents , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Aterosclerose/diagnóstico por imagem , Aterosclerose/mortalidade , Azotemia/diagnóstico por imagem , Azotemia/mortalidade , Azotemia/terapia , Pressão Sanguínea/fisiologia , Creatinina/sangue , Feminino , Seguimentos , Humanos , Hipertensão Renovascular/diagnóstico por imagem , Hipertensão Renovascular/mortalidade , Hipertensão Renovascular/terapia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which regulates proliferation and apoptosis in organ development. YAP function has been extensively characterized in epithelial cells and tissues, but its function in adult skeletal muscle remains poorly defined. Here we show that YAP positively regulates basal skeletal muscle mass and protein synthesis. Mechanistically, we show that YAP regulates muscle mass via interaction with TEAD transcription factors. Furthermore, YAP abundance and activity in muscles is increased following injury or degeneration of motor nerves, as a process to mitigate neurogenic muscle atrophy. Our findings highlight an essential role for YAP as a positive regulator of skeletal muscle size. Further investigation of interventions that promote YAP activity in skeletal muscle might aid the development of therapeutics to combat muscle wasting and neuromuscular disorders.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Western Blotting , Proteínas de Ciclo Celular , Denervação , Feminino , Células HEK293 , Via de Sinalização Hippo , Humanos , Hipertrofia , Masculino , Camundongos Endogâmicos C57BL , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Degeneração Neural/patologia , Tamanho do Órgão , Fosfoproteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima , Proteínas de Sinalização YAPRESUMO
The object of this study was to examine whether eating behavior, food preference, gastric emptying, and gut hormone patterns are altered after jejunoileal bypass (JIB) in patients with severe obesity. Eight obese [mean (+/- SD) body mass index (BMI; in kg/m2) 42.9 +/- 4] subjects were studied prospectively before and 9 mo after JIB with eight age- and sex-matched normal-weight control subjects. Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied. BMI was reduced by 29% after JIB. Compared with normal subjects, the JIB patients showed a reduced desire to eat, decreased hunger, and reduced prospective consumption before a test meal. After surgery, obese subjects selected fewer food items and showed a reduced preference for high-carbohydrate and high-fat items before a test meal. There was a trend from an accelerated toward a decelerated eating pattern in obese subjects after JIB. After JIB, gastric emptying of obese subjects was slowed and similar to that in control subjects. Obese subjects had lower postprandial cholecystokinin concentrations that were lower than those of control subjects both before and after JIB. Postprandial concentrations of neurotensin were higher after JIB. We conclude that after JIB, the desire to eat and preference for high-carbohydrate and high-fat items is reduced, resulting in decreased energy intake. That gastric emptying is prolonged and gut hormone patterns are altered with low postprandial plasma cholecystokinin and high neurotensin plasma concentrations may at least partly account for these observations.
Assuntos
Ingestão de Alimentos , Preferências Alimentares , Esvaziamento Gástrico , Hormônios Gastrointestinais/sangue , Derivação Jejunoileal , Obesidade/fisiopatologia , Adulto , Sistema Digestório/metabolismo , Ingestão de Alimentos/fisiologia , Ingestão de Alimentos/psicologia , Ingestão de Energia , Feminino , Humanos , Masculino , Obesidade/cirurgia , Período Pós-Operatório , Período Pós-Prandial , Valores de ReferênciaRESUMO
We have previously shown that during percutaneous transluminal renal angioplasty (PTRA) there is a transient increase in plasma renin activity (PRA) that is partly mediated by adrenergic beta-receptors. Despite a concomitant increase in plasma aldosterone, no increase in blood pressure occurred. The aim of this study was to record sympathetic outflow in man during PTRA as reflected by muscle nerve sympathetic activity and arterial plasma noradrenaline. Nine patients with hypertension and unilateral renal artery stenosis underwent PTRA by the Grüntzig technique and simultaneous microelectrode recording of muscle nerve sympathetic activity in the peroneal nerve. Blood pressure and heart rate were recorded and blood specimens were drawn for determination of noradrenaline and PRA. During total occlusion of the renal artery, muscle nerve sympathetic activity and the heart rate were unchanged. In the first 6 min after occlusion PRA increased transiently, but there was no significant change in muscle nerve sympathetic activity, arterial noradrenaline, heart rate or blood pressure. From 10 min after PTRA, muscle nerve sympathetic activity was significantly increased and after 40 min there was a significant increase in noradrenaline. The heart rate remained unchanged throughout the procedure, but the blood pressure decreased progressively and the diastolic blood pressure was significantly reduced at 40 min, indicating successful dilation. Despite activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, two strong pressor systems, the only circulatory reaction was a decrease in diastolic blood pressure. These findings indicate simultaneous activation of a potent depressor mechanism during PTRA.
Assuntos
Angioplastia com Balão , Hipertensão Renovascular/terapia , Músculos/inervação , Nervo Fibular/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Idoso , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Hipertensão Renovascular/sangue , Hipertensão Renovascular/fisiopatologia , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Norepinefrina/sangue , Artéria Renal , Renina/sangueRESUMO
OBJECTIVES: The viscosity of blood is increased in patients with essential hypertension. The aim of the present study was to investigate the importance of the different variables of blood rheology to total peripheral resistance, and to elucidate whether inappropriate regulation of the formation of erythropoietin could be important. DESIGN: Nineteen consecutive patients with untreated essential hypertension were examined and compared with a group of matched healthy volunteers. METHODS: The haemorheologic variables were assessed by rotational viscometry and the haemodynamic variables by bioimpedance cardiography. The serum concentrations of erythropoietin were determined by radioimmunoassay. RESULTS: The whole blood viscosity and peripheral resistance index were elevated in the hypertensive group. The two variables were positively correlated with each other (r = 0.68, P = 0.0015). The plasma viscosity and erythrocyte aggregation tendency were increased and the erythrocyte deformability, measured as fluidity, was decreased in the hypertensive patients. In the male subpopulation (n = 12) the aggregation tendency was positively, and the deformability negatively, correlated with body mass index. The serum concentrations of erythropoietin were equal in the two groups. CONCLUSIONS: The increased total peripheral resistance in patients with essential hypertension may in part be explained by an increased blood viscosity, but the possibility of an opposite cause-effect relationship must also be taken into consideration. The haemorheological abnormalities observed in the present patients cannot be explained by high serum levels of erythropoietin.
Assuntos
Viscosidade Sanguínea , Hipertensão/fisiopatologia , Resistência Vascular , Adulto , Feminino , Hemodinâmica , Hemorreologia , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
OBJECTIVES: To investigate if antihypertensive treatment could improve endothelium-dependent vasodilatation in hypertensive patients, and whether the angiotensin II subtype-1 (AT1)-receptor antagonist irbesartan and the beta1-receptor antagonist atenolol would differ in this respect. SUBJECTS AND METHODS: Thirty-four patients (28 men and six women) with mild-to-moderate essential hypertension (diastolic blood pressure 90-120 mmHg) were randomized to once daily 150-300 mg irbesartan or 50-100 mg atenolol in a double-blind fashion, preceded by a placebo run-in period. Forearm blood flow (FBF) was assessed by venous occlusion plethysmography during local intra-arterial infusions of methacholine and sodium nitroprusside, to evaluate endothelium-dependent and endothelium-independent vasodilatation, respectively. Measurements of FBF were undertaken at the end of the run-in placebo period and repeated after 3 months of active antihypertensive treatment. RESULTS: Irbesartan and atenolol induced a similar decline in blood pressure (from 171/107 to 158/98 mmHg, P < 0.05), and improved endothelium-dependent vasodilatation (e.g. an increase in FBF response to 4 microg/min methacholine from 325 +/- 29% to 411 +/- 41%, P < 0.05), with no difference between the two study drugs. No significant changes in endothelium-independent vasodilatation were induced by irbesartan or by atenolol. CONCLUSIONS: The present study shows that 3 months of antihypertensive therapy with irbesartan or atenolol improves endothelium-dependent vasodilatation.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Tetrazóis/uso terapêutico , Antagonistas de Receptores de Angiotensina , Método Duplo-Cego , Feminino , Antebraço/irrigação sanguínea , Humanos , Irbesartana , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina , Fluxo Sanguíneo Regional/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.
Assuntos
Antagonistas de Receptores de Angiotensina , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético/fisiologia , Tetrazóis/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Atenolol/uso terapêutico , Método Duplo-Cego , Feminino , Previsões , Humanos , Irbesartana , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina , Resultado do TratamentoRESUMO
BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.
Assuntos
Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Tetrazóis/uso terapêutico , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Atenolol/efeitos adversos , Atenolol/uso terapêutico , Compostos de Bifenilo/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Irbesartana , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina , Segurança , Tetrazóis/efeitos adversos , Resistência Vascular/efeitos dos fármacosRESUMO
Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.
Assuntos
Anticoagulantes/administração & dosagem , Glicina/análogos & derivados , Tromboflebite/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Azetidinas , Benzilaminas , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Glicina/farmacocinética , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Trombina/antagonistas & inibidores , Tromboflebite/fisiopatologia , Resultado do TratamentoRESUMO
The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study. First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4 microg/min). Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the response to either MCh or SNP. The improvement in vasodilator response to MCh induced by captopril was closely related to the reduction in BP (r = 0.72, P < 0.01). Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4 microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/-13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after administration of captopril, but not nifedipine. In addition, a significant beneficial effect on EDV was seen in a small pilot study during long-term treatment with captopril.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Nifedipino/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Artérias/fisiopatologia , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Captopril/uso terapêutico , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Antebraço/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Vasodilatadores/uso terapêuticoRESUMO
The increased viscosity of blood of hypertensive patients can be assumed to be a risk factor for the development of cardiovascular diseases. The aim of the present study was to elucidate whether anti-hypertensive treatment has any impact on blood rheology. Twenty patients with previously untreated hypertension who consecutively attended our outpatient hypertension clinic were included in this prospective, open, cross-over study. The patients were randomly selected to treatment with amlodipine or metoprolol. The anti-hypertensive therapy was switched after 4 months. Haemorheological and haemodynamic variables were measured with rotational viscometry and impedance cardiography, respectively. Fifteen and 16 patients could be evaluated after amlodipine or metoprolol treatment respectively. The mean blood pressure (BP) decreased from 159 +/- 22/105 +/- 7 to 139 +/- 21/91 +/- 6 mm Hg on amlodipine and from 162 +/- 22/104 +/- 5 to 145 +/- 24/90 +/- 8 mm Hg on metoprolol therapy. After amlodipine treatment, the total peripheral resistance index decreased whereas metoprolol treatment was accompanied by a decrease in the cardiac index. Decreases in whole blood viscosity, haematocrit and serum erythropoietin were found after amlodipine as well as metoprolol treatment. After amlodipine the plasma viscosity decreased and the erythrocyte deformability increased in the majority of patients. Plasma fibrinogen decreased after metoprolol treatment. Despite the differences in haemodynamic mechanisms underlying the decrease in BP, amlodipine and metoprolol exert beneficial effects on blood viscosity. Haemodilution and a decrease in serum erythropoietin may be factors underlying this decrease in blood viscosity.
Assuntos
Anlodipino/farmacologia , Viscosidade Sanguínea/efeitos dos fármacos , Eritropoetina/sangue , Hipertensão/tratamento farmacológico , Metoprolol/farmacologia , Adulto , Idoso , Anlodipino/uso terapêutico , Contagem de Células Sanguíneas/efeitos dos fármacos , Análise Química do Sangue , Estudos Cross-Over , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Metoprolol/uso terapêutico , Pessoa de Meia-IdadeRESUMO
Insulin is known to increase blood flow in parallel to glucose uptake in skeletal muscle. However, it is not known if an increase in blood flow by itself is associated with an increase in glucose uptake in the absence of hyperinsulinemia. To investigate further this matter, the effect of increased blood flow on forearm glucose uptake was studied in the fasting state during intra-arterial infusions of two different vasodilators, metacholine and nitroprusside, in 19 hypertensive subjects. Both metacholine (4 microg/min) and nitroprusside (10 microg/min) increased resting forearm blood flow, measured by venous occlusion plethysmography, to a similar degree (180 % and 170 %, respectively, p<0.0001 for both). However, metacholine infusion increased the forearm glucose uptake from 2.0+/-0.9 (S.D.) during rest to 5.5+/-3.0 umol/min/100 ml tissue (p<0.0001), while no significant change in glucose uptake was seen during nitroprusside infusion (2.3+/-1.4 micromol/min/100 ml tissue). In conclusion, vasodilatation induced by metacholine, but not by nitroprusside, increased glucose uptake in the forearm of hypertensive patients. Thus, an increase in forearm blood flow does not necessarily improve glucose uptake in the forearm during the fasting state.
Assuntos
Glicemia/metabolismo , Antebraço/irrigação sanguínea , Cloreto de Metacolina/farmacologia , Nitroprussiato/farmacologia , Vasodilatadores/farmacologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Jejum , Humanos , Hipertensão/fisiopatologia , Cinética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Consumo de OxigênioRESUMO
Whole blood viscosity, plasma viscosity, erythrocyte deformability, and finger systolic pressure (FSP) were measured in ten patients with primary vasospastic (Raynaud's) disease before and after a controlled double-blind prospective trial involving dazoxiben (a thromboxane inhibitor, Pfizer). Five of the patients were assigned to dazoxiben and five to placebo. Before treatment, the FSP at 10 degrees C in the patient groups was significantly lower than that in a normal reference group, but all rheologic variables, measured at 37 and 10 degrees C, were normal. There was no significant correlation between FSP and rheology. Dazoxiben did not yield any subjective relief or give any objective effect.
Assuntos
Viscosidade Sanguínea/efeitos dos fármacos , Imidazóis/uso terapêutico , Contração Miocárdica/efeitos dos fármacos , Doença de Raynaud/tratamento farmacológico , Sístole/efeitos dos fármacos , Adulto , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Dedos/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença de Raynaud/fisiopatologia , Tromboxano-A Sintase/antagonistas & inibidoresRESUMO
The acute hemodynamic response to captopril (8 patients) and enalapril (8 patients) was evaluated in congestive heart failure patients in NYHA functional class III. All patients had a history of congestive heart failure for more than six months. The results show marked interindividual variations but average values for cardiac output increase and decrease in filling pressures agree with findings in the literature. 6 patients in the captopril group and five in the enalapril group were started on maintenance therapy. One patient in the captopril group deteriorated and underwent a successful heart transplantation and one patient in the enalapril group returned with arrhythmias and hypertension (probably not drug-related) after 48 h of therapy. Our data indicate that activation of the renin-angiotensin system through excessive administration of loop-diuretics is associated with a risk of hypovolemia and thus drug-induced hypotension that deserves special attention when considering converting enzyme inhibitor therapy in congestive heart failure.
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Administração Oral , Captopril/uso terapêutico , Dipeptídeos/uso terapêutico , Enalapril , Teste de Esforço , Furosemida/uso terapêutico , Humanos , Hipertensão/tratamento farmacológicoRESUMO
PURPOSE: To prospectively compare the diagnostic accuracy of duplex ultrasonography, captopril renography, computed tomography angiography (CTA), and 3D Gd magnetic resonance angiography (MRA) in diagnosing hemodynamically significant renal artery stenosis (RAS). MATERIAL AND METHODS: The standard of reference was measurement of transstenotic pressure gradient. Fifty-eight hypertensive patients with suspicion of RAS were evaluated, when possible, by all five techniques. Sensitivity and specificity to detect RAS were compared for each technique on both a patient and kidney basis. Discrepancies were evaluated separately and classified as borderline, method dependent, or operator dependent. RESULTS: The prevalence of RAS was 77%. The sensitivity/specificity of ultrasonography, captopril renography, CTA, and MRA in detecting kidneys with RAS was 73/71%, 52/63%, 94/62%, and 93/91%, respectively. Ultrasonography had a significantly lower sensitivity than CTA and MRA (P<0.001) but higher than captopril renography (P = 0.013). Borderline RAS was the main cause for discrepancies. CONCLUSION: MRA and CTA were significantly better than duplex ultrasonography and captopril renography in detecting hemodynamically significant RAS. The ultrasonography criteria for RAS based on the evaluation of renal peak systolic velocity and renal/aortic ratio are questionable. Captopril renography cannot be recommended for assessing RAS.